This application is related to provisional application No. 60/027,480, which is incorporated by reference in its entirety.
The invention relates to a process for the production of epothilones and intermediate products within the process.
Epothilones 1 (DE 41 38 042) represent a new class of tubulin-stabilizing natural substances with taxol-like action. Bollag, Cancer Research, 1995, Bd. 55, pp. 2325-2333. Their cytotoxic action with regard to pharmaceutical agent-resistant tumor cell lines is of especially great importance for use in cancer treatment [G. Hofle, N. Bedorf, H. Steinmetz, D. Schomburg, K. Gerth, H. Reichenbach Angew. Chem. [Applied Chemistry] 1996, 108, 1671; Angew. Chem. Int. Ed. Engl. 1996, 35, 1567; D. Schinzer "Epothilones--New Promising Microtubule-Stabilizing Natural Products with Taxol-like Biological Activity," Eur. Chem. Chron. 1996, 1, 7; D. M. Bollag, P. A. McQueney, J. Zhu, O. Hensens, L. Koupal, J. Liesch, M. Goetz, E. Lazarides, C. M. Woods, Cancer Res. 1995, 55, 2325].
Epothilones 1 (A: R.dbd.H, B: R.dbd.Me) were recently isolated from myxobacteria and are accessible by fermentation. Because of their very advantageous biological properties, the synthesis of epothilones is of greatest importance.